Type of Renal Replacement Therapy and Residual Renal Function May Affect Prohepcidin and Hepcidin

Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation.?Methods.?Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers.?Results.?In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 ± 95.84 vs. 341.84 ± 90.45 ng/mL, p < 0.01; 142.76 ± 57.87 vs. 238.42 ± 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 ± 89.87 vs. 295.76 ± 129.65 ng/mL, p < 0.01; 108.43 ± 75.49 vs. 186.53 ± 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients.?Conclusions.?Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration.     

Hyporesponsiveness to Erythropoietin Therapy in Hemodialyzed Patients: Potential Role of Prohepcidin,Hepcidin, and Inflammation

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFα and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFα, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.     

Serum prohepcidin levels and iron parameters in term small-for gestational age newborns

Abstract

Aim.?To understand the effect of prenatal chronic hypoxia on prohepcidin levels in term newborns.

Method.?We determined prohepcidin (Pro-Hep) levels in both term appropriate-for-gestational age (AGA) and term small-for-gestational-age (SGA) infants. Uteroplacental insufficiency had exposed all SGA infants to chronic hypoxia. Serum samples were collected from nine full-term SGA infants. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and prohepcidin levels.

Results.?The mean serum Pro-Hep level was 156.4 ± 46.7 ng/ml for SGA infants and 482 ± 371.9 ng/ml for 16 healthy term AGA infants (historical controls); this difference was statistically significant. Statistical analyses revealed significant between-group differences for hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum ferritin and Pro-Hep levels.

Conclusion.?This study showed that compared with AGA infants, Pro-Hep levels were lower in term SGA infants, suggesting that prenatal chronic hypoxia decreases Pro-Hep synthesis.     

Umbilical Blood Flow Correlated to Maternal Hemodynamics in Severe Preeclampsia

Objective: The objective of the study was to compare pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), C-reactive protein (CRP), IL-6 and iron status parameters in preeclamptic (PE) and healthy pregnant women, and to examine the relationship between serum pro-hepcidin levels and iron parameters of preeclampsia (PE). Methods: In a prospective controlled study, we collected serum from women with normal pregnancy (n?=?37) and from women with PE (n?=?30) at the Department of Obstetrics and Gynecology at Turgut Ozal University between February 2010 and January 2013. Pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), CRP, IL-6 and iron status parameters were measured in all patients and compared between groups. Results: Levels of serum prohepcidin in PE and control groups were similar and amount 69.4?±?19.7 and 71.9?±?22.1?ng/ml, respectively. The difference was not statistically significant (p: 0.694). On the other hand, the study group had a statistically lower iron binding capacity (IBC), total iron binding capacity, transferin, total protein, albumin levels (p?<?0.05). No significant differences were found among prohepcidin, Hb concentration, Hct, iron, ferritin, IL-6, urea and creatine in both the groups. Conclusion: In pregnancies complicated by PE with normal values of hemoglobin and hematocrit, serum prohepcidin concentrations are similar to those observed in healthy pregnant women. The analysis revealed no significant correlations between prohepcidin level and serum iron, serum ferritin or transferrin in the PE.     

Prohepcidin levels during human perinatal adaptation

The aim of this study was to test for the presence of prohepcidin in cord blood, to gauge its alteration during the early postnatal period, and to look for a possible association with neonatal iron homeostasis. Cord blood and postnatal venous blood samples were taken from 20 healthy neonates. In both kinds of samples the presence prohepcidin could be detected. No association was found between cord blood and postnatal samples prohepcidin and iron homeostasis. However, an association is demonstrated between cord blood prohepcidin values and mean cell hemoglobin concentration (MCHC). Prohepcidin increased postnatally in half of the neonates, indicating the active synthesis of the molecule. Interestingly, neonates with detectable non-protein-bound iron levels in cord blood were presented with lower prohepcidin concentrations. Association between cord blood prohepcidin and MCHC may suggest a possible link between hepcidin and fetal iron homeostasis.     

Regulatory failure of serum prohepcidin levels in patients with hepatitis C

BACKGROUND/AIMS: Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C (CHC), which may be related to hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed in this study to generate some information about hepcidin in CHC. METHODS: To determine whether serum hepcidin correlates with markers of iron status in patients with viral hepatitis, we measured serum prohepcidin levels in patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy controls. RESULTS: Serum prohepcidin and ferritin levels were negatively correlated (r=-0.182, P=0.037) in HCV patients and positively correlated in HBV patients and in healthy controls. The total iron scores in liver specimens from HCV patients were also negatively correlated (r=-0.403, P=0.013). Serum prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower than in patients with chronic hepatitis (CH). In both CH and LC patients, serum prohepcidin levels were significantly lower in HCV patients than in HBV patients. CONCLUSION: Failure of homeostatic regulation of serum prohepcidin concentrations may be induced by HCV infection, resulting in elevation of serum ferritin levels, which leads to the progression of liver injury by iron overload in CHC patients.